Organ printing

The field of organ printing stemmed from research in the area of stereolithography, the basis for the practice of 3D printing that was invented in 1984. In this early era of 3D printing, it was not possible to create lasting objects because of the material used for the printing process was not durable. 3D printing was instead used as a way to model potential end products that would eventually be made from different materials under more traditional techniques. At this time, a researcher used a modified HP inkjet printer to deposit cells using cytoscribing technology. The scientists at Wake Forest printed an artificial scaffold for a human bladder and then seeded the scaffold with cells from their patient. After the bladder at Wake Forest, strides were taken towards printing other organs. In 2002, a miniature, fully functional kidney was printed. This process utilized a modified spotting system for the deposition of cells into organized 3D matrices placed on a substrate. In 2004, the field of bioprinting was drastically changed by yet another new bioprinter. The printed heart had the correct anatomical structure and function compared to real hearts. This breakthrough represented a real possibility of printing fully functioning human organs. In fact, scientists at the Warsaw Foundation for Research and Development of Science in Poland have been working on creating a fully artificial pancreas using bioprinting technology. As of today, these scientists have been able to develop a functioning prototype. This is a growing field and much research is still being conducted. == 3D printing techniques ==

3D printing for the manufacturing of artificial organs has been a major topic of study in biological engineering. As the rapid manufacturing techniques entailed by 3D printing become increasingly efficient, their applicability in artificial organ synthesis has grown more evident. Some of the primary benefits of 3D printing lie in its capability of mass-producing scaffold structures, as well as the high degree of anatomical precision in scaffold products. This allows for the creation of constructs that more effectively resemble the microstructure of a natural organ or tissue structure. Organ printing using 3D printing can be conducted using a variety of techniques, each of which confers specific advantages that can be suited to particular types of organ production. Sacrificial writing into functional tissue (SWIFT) Sacrificial writing into function tissue (SWIFT) is a method of organ printing where living cells are packed tightly to mimic the density that occurs in the human body. While packing, tunnels are carved to mimic blood vessels and oxygen and essential nutrients are delivered via these tunnels. This technique pieces together other methods that only packed cells or created vasculature. SWIFT combines both and is an improvement that brings researchers closer to creating functional artificial organs. Drop-based bioprinting (Inkjet) Drop-based bioprinting makes cellular developments utilizing droplets of an assigned material, which has oftentimes been combined with a cell line. Cells themselves can also be deposited in this manner with or without polymer. When printing polymer scaffolds using these methods, each drop starts to polymerize upon contact with the substrate surface and merge into a larger structure as droplets start to coalesce. Polymerization can happen through a variety of methods depending on the polymer used. For instance, alginate polymerization is started by calcium ions in the substrate, which diffuse into the liquified bioink and permit for the arrangement of a strong gel. Drop-based bioprinting is commonly utilized due to its productive speed. However, this may make it less appropriate for more complicated organ structures. Extrusion bioprinting Extrusion bioprinting includes the consistent statement of a specific printing fabric and cell line from an extruder, a sort of portable print head. This tends to be a more controlled and gentler handle for fabric or cell statement, and permits for more noteworthy cell densities to be utilized within the development of 3D tissue or organ structures. In any case, such benefits are set back by the slower printing speeds involved by this procedure. Extrusion bioprinting is coupled with UV light, which photopolymerizes the printed fabric to create a more steady, coordinated construct. The laser traces a cross-section of the shape of the desired object in the powder, which fuses it together into a solid form. A new layer of powder is then laid down and the process repeats itself, building each layer with every new application of powder, one by one, to form the entirety of the object. One of the advantages of SLS printing is that it requires very little additional tooling, i.e. sanding, once the object is printed. Recent advances in organ printing using SLS include 3D constructs of craniofacial implants as well as scaffolds for cardiac tissue engineering. ==Printing materials==

Printing materials must fit a broad spectrum of criteria, one of the foremost being biocompatibility. The resulting scaffolds formed by 3D printed materials should be physically and chemically appropriate for cell proliferation. Biodegradability is another important factor, and insures that the artificially formed structure can be broken down upon successful transplantation, to be replaced by a completely natural cellular structure. Due to the nature of 3D printing, materials used must be customizable and adaptable, being suited to wide array of cell types and structural conformations. Natural polymers Materials for 3D printing usually consist of alginate or fibrin polymers that have been integrated with cellular adhesion molecules, which support the physical attachment of cells. Such polymers are specifically designed to maintain structural stability and be receptive to cellular integration. The term bio-ink has been used as a broad classification of materials that are compatible with 3D bioprinting. Hydrogel alginates have emerged as one of the most commonly used materials in organ printing research, as they are highly customizable, and can be fine-tuned to simulate certain mechanical and biological properties characteristic of natural tissue. The ability of hydrogels to be tailored to specific needs allows them to be used as an adaptable scaffold material, that are suited for a variety of tissue or organ structures and physiological conditions. A major challenge in the use of alginate is its stability and slow degradation, which makes it difficult for the artificial gel scaffolding to be broken down and replaced with the implanted cells' own extracellular matrix. Alginate hydrogel that is suitable for extrusion printing is also often less structurally and mechanically sound; however, this issue can be mediated by the incorporation of other biopolymers, such as nanocellulose, to provide greater stability. The properties of the alginate or mixed-polymer bioink are tunable and can be altered for different applications and types of organs. These qualities are advantageous and result in high acceptance of the 3D bioprinted organ when implanted in vivo. == Types of printers and processes ==

The types of printers used for organ printing include: • Inkjet printer • Multi-nozzle • Hybrid printer • Electrospinning • Drop-on-demand These printers are used in the methods described previously. Each printer requires different materials and has its own advantages and limitations. == Applications ==

Organ donation Currently, the sole method for treatment for those in organ failure is to await a transplant from a living or recently deceased donor. In the United States alone, there are over 100,000 patients on the organ transplant list waiting for donor organs to become available. Patients on the donor list can wait days, weeks, months, or even years for a suitable organ to become available. The average wait time for some common organ transplants are as follows: four months for a heart or lung, eleven months for a liver, two years for a pancreas, and five years for a kidney. This is a significant increase from the 1990s, when a patient could wait as little as five weeks for a heart. In the United States, 20 people die everyday waiting for organs. In the field of organ printing, applications can be applied for patients and surgeons. For instance, printed organs have been used to model structure and injury to better understand the anatomy and discuss a treatment regime with patients. For these cases, the functionality of the organ is not required and is used for proof-of-concept. These model organs provide advancement for improving surgical techniques, training inexperienced surgeons, and moving towards patient-specific treatments. These organs-on-chips have the potential to be used for disease models, aiding in drug discovery, and performing high-throughput assays. The new body-on-a-chip platform includes liver, heart, lungs, and kidney-on-a-chip. The organs-on-a-chip are separately printed or constructed and then integrated together. Using this platform drug toxicity studies are performed in high throughput, lowering the cost and increasing the efficiency in the drug-discovery pipeline. == Legal and safety ==

3D-printing techniques have been used in a variety of industries for the overall goal of fabricating a product. Organ printing, on the other hand, is a novel industry that utilizes biological components to develop therapeutic applications for organ transplants. Due to the increased interest in this field, regulation and ethical considerations desperately need to be established. Specifically, there can be legal complications from pre-clinical to clinical translation for this treatment method. Regulation The current American regulation for organ matching is centered on the national registry of organ donors after the National Organ Transplant Act was passed in 1984. In 2016, the FDA issued draft guidance on the Technical Considerations for Additive Manufactured Devices and is currently evaluating new submissions for 3D printed devices. However, the technology itself is not advanced enough for the FDA to mainstream it directly. The cell sources mentioned previously also need to be considered. Organ printing can decrease or eliminate animal studies and trials, but also raises questions on the ethical implications of autologous and allogenic sources. More specifically, studies have begun to examine future risks for humans undergoing experimental testing. Generally, this application can give rise to social, cultural, and religious differences, making it more difficult for worldwide integration and regulation. Overall, the ethical considerations of organ printing are similar to those of general ethics of bioprinting, but are extrapolated from tissue to organ. Altogether, organ printing possesses short- and long-term legal and ethical consequences that need to be considered before mainstream production can be feasible. == Impact ==

Organ printing for medical applications is still in the developmental stages. Thus, the long term impacts of organ printing have yet to be determined. Researchers hope that organ printing could decrease the organ transplant shortage. There is currently a shortage of available organs, including liver, kidneys, and lungs. The lengthy wait time to receive life saving organs is one of the leading causes of death in the United States, with nearly one third of deaths each year in the United States that could be delayed or prevented with organ transplants. The bladder was formed from the host's bladder tissue. Animal testing is used to determine the safety of products ranging from makeup to medical devices. Cosmetic companies are already using smaller tissue models to test new products on skin. An additional impact of organ printing includes the ability to rapidly create tissue models, therefore increasing productivity. == Challenges ==

One of the challenges of 3D printing organs is to recreate the vasculature required to keep the organs alive. Designing a correct vasculature is necessary for the transport of nutrients, oxygen, and waste. Additional challenges include designing clinical trials to test the long-term viability and biocompatibility of synthetic organs. While many developments have been made in the field of organ printing, more research must be conducted. == References ==